BIOTECH CAPITAL - Proactiveinvestors UK€¦ · RGA 89, 136, 190 RGA 28, 42, 86 RGA 142, 197, 64 RGA 167, 193, 221 RGA 132, 152, 214 RGA 197, 224, 180 C4XD.L BIOTECH CAPITAL

www.c4xdiscovery.com

RGA 89, 136, 190

RGA 28, 42, 86

RGA 142, 197, 64

RGA 167, 193, 221

RGA 132, 152, 214

RGA 197, 224, 180

C4XD.L

BIOTECH CAPITAL London, UK

Dr Craig Fox, Chief Scientific Officer

3rd MARCH 2016

Better, Safer, Faster Better, Safer, Faster Better, Safer, Faster

FORWARD-LOOKING STATEMENT

This presentation includes statements that are, or may be, “forward-looking statements”. These statements relate to, among other things, analyses and other information based on forecasts of future results and estimates which are not yet determinable. These forward-looking statements are sometimes identified by the use of terms and phrases such as "believe", "expects", "envisage", "may", "will", "could", "should", "shall", "risk", "intends", "estimates", "aims", "plans", "predicts", "continues", "assumes", "positioned", "targets" or "anticipates" or the negative thereof, variations or comparable expressions, including reference to assumptions. These forward-looking statements include all matters that are not historical facts. They appear in a number of places throughout this presentation. The forward-looking statements, including statements regarding projections of the Company’s future results, operations, profits and earnings are based on the Directors' current expectations projections, and assumptions and involve known and unknown risks, uncertainties and other factors that may cause the actual results, financial condition, performance or achievements of the Company or industry results to be materially different from any future results, performance or achievement expressed or implied by such forward looking. Given such risks and uncertainties no reliance should be placed on any forward-looking statement. New factors may emerge from time to time that could cause the Company's business not to develop as it expects and it is not possible for the Company to predict all such factors. Each forward-looking statement contained in this presentation speaks only as of the date of the particular statement. The Company, the Directors and the Company’s associates expressly disclaim any obligation to update these forward-looking statements contained in this presentation to reflect any change in their expectations or any change in future events or developments on which such statements are based unless required to do so by applicable law or regulation or the AIM Rules for Companies.

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C4XD AIMS TO BECOME THE WORLD’S MOST PRODUCTIVE DRUG DISCOVERY ENGINE COMBINING CUTTING-EDGE TECHNOLOGIES WITH AN EXPERIENCED MANAGEMENT TEAM

C4XD INTRODUCTION

STRENGTH OF MANAGEMENT team with track record of value creation

HUMAN GENETICS PLATFORM that provides proprietary target discovery & validation to ‘fuel’ the discovery engine (“Taxonomy3®”)

UNIQUE DRUG DISCOVERY ENGINE utilising in vitro 3D drug shapes with unique software (“Conformetrix”) discovering more potent drugs faster

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Better, Safer, Faster Better, Safer, Faster

Better, Safer, Faster

C4XD AIMS TO BECOME THE WORLD’S MOST PRODUCTIVE DRUG DISCOVERY ENGINE COMBINING CUTTING-EDGE TECHNOLOGIES WITH AN EXPERIENCED MANAGEMENT TEAM

HYBRID BUSINESS MODEL of wholly owned pipeline of discovery programmes plus partnerships with Pharma and Biotech

SMALL MOLECULE DRUG design and creation of best-in-class molecules including switch of clinically validated biologic based therapies (mAbs, peptides)

HIGH UNMET MEDICAL NEED across multiple broad therapeutics areas to be targeted and exploited by C4XD’s cutting-edge technologies

C4XD INTRODUCTION

GOALS TO REDUCING cost and time of early stage drug discovery process, driving productivity

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MANAGEMENT TEAM & BOARD

MANAGEMENT

Clive Dix Executive Chairman – serially successful entrepreneur in UK biotech

Brad Hoy Interim-CFO – Ex e-Therapeutics, Plethora,

Craig Fox CSO – Ex Pulmagen, Argenta, Bayer

Charles Blundell CTO – Founder, ex Oxford & Manchester Universities

Thorsten Nowak VP Structural Design & Medicinal Chemistry, ex AstraZeneca

Martin Watson VP Structural Analysis, ex AstraZeneca

Alun McCarthy VP Novel Target Biology & Genomics – Ex Adorial, GSK

Olivier Delrieu VP Clinical Development & Mathematics – Ex Adorial, GSK

NON-EXECUTIVE DIRECTORS

Alex Stevenson Serially successful investor in UK biotech

Harry Finch Senior industry medicinal chemist, > 30 years’ track-record

Sam Williams Head of Biotech, IP Group, top-ranked healthcare analyst

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SIGNIFICANT SHAREHOLDERS:

CURRENT SHAREHOLDER BASE

Name Percentage of issued share capital

The Aquarious IV Fund LLP 14.97%

Aviva plc & its subsidiaries 9.54%

Charles Blundell 9.34%

Andrew Almond 9.26%

The Aquarious Origin Fund LLP 7.99%

Andrew Black 7.69%

Baillie Gifford & Co 6.81%

The percentage of AIM securities not in public hands is 60.97% Directors have 8.06%

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C4XD AIM IPO OCTOBER 2014

Oct 2014 (£11m)

Evaluate GLP-1 Diabetes programme opportunity Oral small molecule equivalent of marketed injectable

Oral Orexin-1 antagonist programme for Addiction Progress leads generated into pre-clinical development

Initiate Nrf-2 activator programme Develop an oral candidate for Inflammatory diseases

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C4XD MARCH 2016

Mar 2016

Leads identified for GPR142 agonist programme Novel oral small molecule target for diabetes

Oral Orexin-1 antagonist programme Currently in pre-clinical development

Leads identified for oral Nrf-2 activator programme Lead optimisation stage to be initiated Q2 2016

Hits/Leads identified for oral GLP-1 diabetes programme Novel lead molecules active in vitro

Hit to Lead stage reached for anti-IL-17 programme Small molecule oral anti-inflammatory (psoriasis)

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C4XD.L

CURRENT PIPELINE


Evaluation Hit to lead Lead

Generation Pre-Clinical Candidate

PORTFOLIO MARCH 2016

Lead Optimisation

IND Ready

Addiction (Orexin-1)

COPD (NRF-2)

Diabetes (GRP142)

Diabetes (GLP-1)

Psoriasis (IL-17)

Taxonomy3 (Target 1)

Oncology (SGC Collab.)

C4XD AIMS TO INCREASE THE NUMBER OF PIPELINE PROGRAMMES >3 FOLD BY 2019

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C4XD CURRENT PIPELINE – HIGHLY VALUABLE MARKETS

1.Market size in 2018; Source: GBI Research 2012 2.Market size in 2017; Source: Visiongain, Asthma and COPD Therapies: World Market 2013-2023 3.Market size in 2017; Source: Visiongain, Diabetes-Treatments-World-Drug-Market-2013-2023 4.Market size in 2018; Source Visiongain, Psoriasis Treatment; Decision Resources;

ADDICTION DIABETES INFLAMMATION

OREXIN-1 ANTAGONIST ($13bn)1

GPR142 AGONIST ($55bn) 3

NRF-2, COPD ($41bn) 2

GLP-1 AGONIST ($55bn) 3

ANTI-IL-17, PSORIASIS ($13bn) 4

Hot GPCR targets lacking target protein crystal structure at project initiation

Marketed Biologics (clinically validated) with small molecule opportunity

Intracellular target protein structure available, novel hit finding less successful with conventional screening but enabled by C4X

ONCOLOGY

SGC COLLABORATION (Initiated Nov 15)

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ADDICTION – ORAL OREXIN 1 ANTAGONIST

Orexin 1 receptor thought to be central to the brain’s ‘craving’ pathway with pre-clinical efficacy observed in multiple addiction models

SUBSTANTIAL MARKET SEGMENTS WITH PATH TO PRODUCT ESTABLISHED

Primary Indication: Nicotine addiction (smoking cessation) • Market leader Chantix

(varenicline) effective on quit rates but minimal prevention of relapse & black box warning on label

Oral Orexin 1 antagonists aim to deliver superior clinical benefit with a much improved safety profile • AZ/Eolas Orexin-1 antagonist

$145m deal July 2015 • Other markets include alcohol

addiction, panic

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COPD – ORAL NRF-2 (ANTI-OXIDANT & ANTI-INFLAMMATORY)

COPD is a $41 bn market with a significant need for effective anti-inflammatory therapy that can be added to bronchodilator therapy as disease severity progresses

PROVEN CLINICAL & REGULATORY DEVELOPMENT PATH IN COPD FOR AN ORAL ANTI-INFLAMMATORY THERAPY

Daliresp (roflumilast) (PDE4 inhibitor, AstraZeneca) • Effective on exacerbation rates

but disappointing degree of efficacy

Oral Nrf-2 activators have the potential to be more efficacious on exacerbation rate and quality of life in COPD with much better tolerability profile • Human genetic and animal model target validation for Nrf-2 in COPD

Reduction in the rate of Moderate or Severe exacerbations

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1.37 1.14

Placebo

(n=1554) Daliresp (n=1537)

0

0.5

1.0

1.5 17% REDUCTION

P=0.0003 vs placebo

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Psoriasis is a $9 bn market with the anti-IL-17 injectable antibody therapy Cosentyx® (Novartis) approved Jan 2015, others in Ph III

PSORIASIS – ORAL & TOPICAL IL-17 INHIBITOR

IL-17 implicated in multiple other inflammatory disorders. Cosentyx recently approved for ankylosing spondylitis & psoriatic arthritis

Oral small molecule inhibitors of IL-17 will offer significant advantages

• Novartis/Ensemble macrocycle deal Aug 2013

PROVEN CLINICAL & REGULATORY DEVELOPMENT PATH IN PSORIASIS, PSORIATIC ARTHRITIS & ANKYLOSING SPONDYLITIS FOR ANTI-IL-17 THERAPY

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Type II Diabetes is a $55 bn market with combination therapy routinely prescribed

DIABETES – ORAL GPR142 & GLP-1 AGONISTS

GPR142 agonists – oral small molecule approach to increase insulin secretion in a glucose dependent manner avoiding hypoglycemia & may also stimulate β-cell proliferation

Oral small molecule agonists of GLP-1 – Injectable GLP-1 Victoza has sales of $2.4 bn. Oral drug version would enable combination pill with marketed drugs

PROVEN CLINICAL & REGULATORY DEVELOPMENT PATH IN TYPE II DIABETES – DIFFERENTIATED ORAL PRODUCTS REQUIRED

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C4XD.L

DISCOVERY ENGINE


C4XD NEW PROGRAMME IDENTIFICATION PROCESS

C4X TARGET EVALUATION FUNCTION

HUMAN GENETICS PLATFORM Discover & validate proprietary drug targets using human genetic data (Taxonomy3®)

COMMERCIALLY ATTRACTIVE marketable opportunity with clear clinical & scientific rationale, therapeutic area agonistic

COMPETITIVE PROGRAMME due to being enabled or optimised by C4XD technologies leading to novel, patentable NCEs

SUITABLE FOR PROGRESSION within a ‘virtual pharma’ environment

PARTNER IDENTIFIED TARGET (Structural Genomics Consortium/SME/Large Pharma)

INDUSTRY STANDARD APPROACHES Literature/Patents/Deals

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TAXONOMY3® – DNA-BASED TARGET ID

Unique mathematical approach that significantly increases the sensitivity of detection when mining disease derived DNA databases Co-developed with University of Oxford, allows access of ‘missing heritability’ to generate new genetic insights

Current methods often focus on large effects in the whole population E.g. “one-gene-for-all” approach, not consistent with complex disorder characteristics, limited gene-gene interaction analysis performed

Taxonomy3® will ‘fuel’ the C4X Discovery Engine using this sensitive revolutionary multivariate analysis that will discover & validate best drug targets for diseases with high unmet medical need

Ground-breaking proprietary genetic analysis technology acquired March 2016 to discover & validate best drug targets for range of diseases. Also provides biomarker identification and patient stratification insights.

UNIQUE MATHEMATICS

VALIDATED DRUG TARGETS

CLINICALLY EFFECTIVE DRUGS

NOVEL GENETIC INSIGHTS

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INCREASED SENSITIVITY OF TAXONOMY3® IDENTIFIES MULTIPLE DISEASE TARGETS AND EXPLORERS GENE-GENE INTERACTIONS

TAXONOMY3® – DNA BASED TARGET ID

*Daly et al., Nature Genetics 41 816-9, 2009

CONVENTIONAL UNIVARIATE methodology* generating single peak

TAXONOMY3® MULTIVARIATE methodology generating multiple peaks

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C4XD’s CONFORMETRIX TECHNOLOGY


C4XD ENABLES RATIONAL, ACCELERATED 4D STRUCTURAL DRUG DESIGN USING EXPERIMENTAL RATHER THAN THEORETICAL DATA

C4XD

CONFORMATION

IDENTIFY THE SHAPE DESIGN

THE CHANGES

SAFER, BETTER

MOLECULES

INDUSTRY C4XD

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C4XD’s CONFORMETRICS


C4XD TECHNOLOGY PROVIDES CONFORMATIONAL DATA ON THE 3D SHAPES OF DRUG MOLECULES

PROPRIETARY SOFTWARE &

ANALYSIS

TEAM OF 10 CONFORMET-

RICS ANALYSTS

CONVEN-TIONAL NMR EQUIPMENT

>200 4D STRUCTURES

SOLVED

Quantification of free ligand conformational preferences

by NMR and their relationship to the bioactive

conformation. Blundell CD, Packer MJ and

Almond A, Bioorganic & Medicinal Chemistry,

2013, 21 (17), 4976-87.

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C4XD - APPLICABLE TO ALL DRUG & TARGET CLASSES

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C4XD TECHNOLOGY – RAPID HIT TO LEAD


PRIMARY BIOLOGICAL SCREEN IDENTIFIES WEAK ‘HITS’ (e.g. 3 μM potency)

HIGH POTENCY LEAD – bioactive conformation

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C4XD PROVIDES A COMPETITIVE EDGE IN DRUG DISCOVERY

Conformational drug design enhances Hit to Lead process & significantly reduces the total number of molecules designed and synthesised

Increase likelihood of success to achieve a pre-clinical candidate and reduce the time taken due to lower number of Med Chem design cycles Significantly lower financial cost to select pre-clinical candidate Candidate better designed for target of interest (increased bioactive conformation) accompanied by reduced ‘off-target’ risk (e.g. reduced non-bioactive conformations) Conformational design can provide distinct chemical backup series via ‘scaffold hop’

C4XD technology can enable drug discovery programmes when applied to:

Targets where structural protein data for the target is not yet available Targets where only non-chemical ligands are known (e.g. peptides) Targets where novel hit finding is less successful with conventional small molecule screening

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Global top 10 Pharma

CURRENT COLLABORATIONS

Largest Japanese Pharma Largest European CRO

The SGC is a world leader in public-private partnership that supports the discovery of new medicines through open access research.

The SGC is backed by the Welcome Trust and major pharma including Bayer, Pfizer, Abbvie, Merck, J&J, Boehringer Ingelheim, Novartis and Takeda

Structural Genomic Consortium

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C4XD.L

SUMMARY


Differentiated cutting-edge proprietary software technologies “Taxonomy3®” and “Conformetrix” exploited by an experienced team

C4XD SUMMARY

Hybrid business model of wholly-owned drug pipeline and partnerships with major Pharma and Biotech

Opportunities for first in class in medicines – enabled by C4XD technology

Small molecule switch – oral small molecule versions of marketed biologics

Management team with track record of significant value creation

BUILDING THE WORLD’S MOST PRODUCTIVE DRUG DISCOVERY ENGINE BY EXPLOITING CUTTING-EDGE TECHNOLOGIES TO CREATE BEST-IN-CLASS DRUG MOLECULES

High unmet medical need across multiple broad therapeutics areas to be targeted

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Thank you

www.c4xdiscovery.com

C4XD.L

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BIOTECH CAPITAL - Proactiveinvestors UK€¦ · RGA 89, 136, 190 RGA 28, 42, 86 RGA 142, 197, 64 RGA 167, 193, 221 RGA 132, 152, 214 RGA 197, 224, 180 C4XD.L BIOTECH CAPITAL

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